POS0293 METABOLOMIC IN ANTIPHOSPHOLIPID SYNDROME STRATIFIED PATIENTS ACCORDING TO THEIR THROMBOTIC RISK
Authors: C. Lopez-Pedrera, M. A. Aguirre, I. Sanchez-Pareja, T. Cerdó, L. Muñoz-Barrera, P. Seguí Azpilcueta, C. Merlo, P. Ortiz Buitrago, D. Ruiz, M. C. Ábalos-Aguilera, N. Barbarroja Puerto, R. Ortega Castro, C. Perez-Sanchez
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Antiphospholipid syndrome (APS) is a systemic autoimmune disorder inducing hypercoagulable state that causes arterial, venous, or microvascular thrombosis, atherosclerosis, and pregnancy morbidity. Timely diagnosis and truthful monitoring of disease are decisive to improve the accuracy of therapy. <h3>Objectives</h3> 1. To map metabolic signatures in sera of APS patients and investigate its association with clinical features of the disease. 2. To investigate the short-term effects of <i>in vivo</i> ubiquinol (reduced coenzyme Q10 [Qred]) supplementation. <h3>Methods</h3> Serum nuclear magnetic resonance (NMR) metabolomics (&gt;250 metabolites, Nightingale) covering glycolysis metabolites, amino acids and 130 lipid measures was performed on a cohort of primary APS patients (n=150) and 43 healthy donors (HD). Extensive clinical and analytical profile of recruited subjects was performed. NMR data were analyzed in MetaboAnalyst 5.0 software platform. To evaluate the contribution of metabolomic profiles to disease features, unsupervised machine learning clustering analyses were developed. Separately, 33 APS patients treated with Ubiquinol (Qred, reduced CoQ10, 200 mg/day) as an adjuvant treatment to standard therapy for one month, were also studied. <h3>Results</h3> Fifty-three metabolites were significantly altered in APS patients compared to HCs, involving decreased atheroprotective HDL subsets, sphingomyelins, phospholipids, and histidine, and increased proatherogenic VLDL subsets and fatty acids (MUFA, omega-3). Unbiased hierarchical clustering of metabolomic data identified two patient groups, presenting different metabolomic profiles. Clinically, although no differences were found in terms of age, gender, disease duration, or treatments, patients belonging to cluster 1 (C1) were characterized by higher thrombotic risk status (aGAPSS over 12), and prevalence of triple positivity for antiphospholipid antibody profile than C2 patients. Besides, C1 patients showed preponderance of arterial thrombosis, and comprised APS patients with higher CV risk (elevated incidence of atheroma plaques, dyslipidemia, obesity, and hypertension). One hundred and forty-three metabolites were found deregulated between clusters. Thus, compared to C2, C1 had decreased atheroprotective HDL and increased atherogenic VLDL and LDL lipoproteins, increased triglycerides, fatty acids, apolipoproteins (ApoB), glycolysis related metabolites (glucose and pyruvate), amino acids (Leu, Tyr, Val, Phe, Ile), inflammation related metabolites (GlycA), and other lipids involved in immune cells activity, such as phosphatidylcholines, sphingomyelins, phosphoglycerides, and cholines. Of note, 28 metabolites were found altered in patients with thrombosis. Logistic regression analyses identified several metabolites which levels distinguished thrombotic APS patients with high accuracy, including VLDL and HDL subsets, fatty acids, amino acids, glucose and creatinine, all reportedly associated to enhanced CV risk. <i>In vivo</i>, Qred supplementation of APS patients partially reversed the altered serum metabolic profile linked to the development of atherosclerosis and thrombosis. <h3>Conclusion</h3> 1. APS patients have a distinctive metabolomic profile, with abnormalities associated with the pathogenesis of the disease, which are partially modified in vivo by Qred supplementation. 2. We have identified for the first time a metabolomic fingerprint able to stratify APS disease according to their thrombotic risk, which might pave the way for the development of new tools to improve their clinical management. Supported by ISCIII: (PI21/0591), and RICORS (RD21/0002/0033) co-financed by FEDER. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None declared.